Phenoxy imidates

ABSTRACT

Novel imidates, intermediates therefor, synthesis thereof and the use of said imidates for the control of pests.

This is a division of application Ser. No. 102,050, filed Dec. 10, 1979.

This invention relates to novel imidates, intermediates therefor,synthesis thereof and the use of said imidates for the control of pests.

The compounds of the present invention are represented by the followingformula (A): ##STR1## wherein,

R is hydrogen, lower alkyl, phenyl or substituted phenyl; ##STR2## where

R³ is lower alkyl, lower haloalkyl, lower alkenyl or lower haloalkenyland R⁴ is the group ##STR3## in which t is zero, one, two, three orfour; Y is independently selected from hydrogen, lower alkyl, lowerfluoroalkyl, lower alkoxy, lower alkylthio, lower alkylcarbonyl, loweralkoxycarbonyl, halogen, and lower fluoroalkylthio; and Z isindependently selected from the values of Y, cycloalkyl, and lowerfluoroalkoxy; or Y and Z form a methylenedioxy group; and ##STR4##

The compounds of the present invention represented by formula (A) areuseful agents for the control of pests such as insects and acarids.

In the description hereinafter and the appended claims, each of Rthrough R⁴, t, Y and Z is defined hereinabove, unless otherwisespecified.

The compounds of formula (A) can be synthesized as outlined below.##STR5##

In the general practice of the above synthesis, the acid chloride madefrom reaction of the carboxylic acid (I) and oxalyl chloride, is reactedwith an amine NH₂ --R. The resulting amide (II) is then reacted with ahalide R² --X (X is bromo or chloro) in the presence of silvertetrafluoroborate to form the imidate (A).

An alternate method of synthesis of the compounds of the presentinvention, when R is H, can be illustrated as follows (R' is loweralkyl): ##STR6##

In the above general synthesis, the amide (III) is treated with atrialkyloxonium tetrafluoroborate to form the imidate (IV). Upontransesterification, compound IV is converted to the desired imidate(A').

The imidates of formula (IV) wherein R¹ is a phenylamino group can besynthesized also by treatment of a nitrile (V) with HCl or other strongacid in an alcohol R'--OH. ##STR7##

The following terms, wherever used in the description herein and theappended claims, have the meaming defined below, unless otherwisespecified hereinafter.

The term "lower alkyl" refers to an alkyl group, straight or branched,having a chain length of one to six carbon atoms. The term "lowerhaloalkyl" refers to an alkyl group substituted with one to threehalogen atoms such as chloromethyl, fluoromethyl, trifluoromethyl,2,2,2-trifluoroethyl, 6-chlorohexyl, 2-fluoroethyl, and the like. Theterm "lower fluoroalkyl" refers to an alkyl group substituted with oneto three fluorine atoms. The term "lower alkoxy" refers to an alkoxygroup, straight or branched, having a chain length of one to eightcarbon atoms. The term "lower alkylthio" refers to an alkylthio group,straight or branched, having a chain length of one to eight carbonatoms.

The term "cycloalkyl" refers to a cycloalkyl group of three to eightcyclic carbon atoms.

The term "lower alkenyl" refers to an ethylenically unsaturatedhydrocarbon group, straight or branched, having a chain length of two toeight carbon atoms and one or two ethylenic bonds such as vinyl, allyl,3-butenyl, 2-hexenyl, i-propenyl, 2,4-hexadienyl, and the like. The term"lower haloalkenyl" refers to a lower alkenyl group substituted with oneto three halogen atoms.

The term "substituted phenyl" refers to a phenyl group substituted atone, two or three of the ring carbon atoms with a group selected fromlower alkyl, lower fluoroalkyl, lower alkoxy, lower alkenyl, lowerhaloalkenyl, lower alkenyloxy, halogen, nitro, cyano, lower alkylthio,and the like.

The term "lower fluoroalkoxy" refers to a lower alkoxy group substitutedwith one to three fluorine atoms.

The term "lower acyloxy" refers to a lower organic acyloxy group of oneto six carbon atoms, such as acetoxy.

The compounds of the present invention of formula (A) have one or moreasymmetric carbon atoms. The present invention includes each of theoptical isomers and racemic mixtures thereof. In the exampleshereinafter, unless otherwise specified, the compound prepared is aracemic mixture.

The compounds of the present invention of formula A are useful pestcontrol agents, particularly for the control of insects and acarids. Inthe use of the compounds of formula A for combating insects and acaridsfor the protection of agricultural crops, for example, soybeans, cotton,alfalfa, etc., a compound of formula A, or mixtures thereof, togetherwith a carrier is applied to the locus in a pesticidally effectiveamount. The carrier can be liquid or solid and include adjuvants such aswetting agents, dispersing agents and other surface active agents. Thecompounds of formula A can be used in formulations such as wettablepowders, solutions, dusts, granules, emulsifiable concentrates, and thelike. Suitable solid carriers include natural and synthetic silicatesand clays, carbon or charcoal granules, natural and synthetic resins,waxes, and the like. Suitable liquid carriers include water, aromatichydrocarbons, alcohols, vegetable and mineral oils, ketone, and thelike. The amount of a compound of formula A in the formulation can varywidely, generally within th range of about 0.01 percent to about 90.0percent, by weight.

The compounds of the present invention are effective on many differentinsects and on acarids. The compounds are effective control agents forinsects such as mosquitoes, flies, aphids, weevils and acarids such asthe spider mite and ticks. Depending upon the particular combination ofthe substituents of formula (A) herein, the compounds have a broad orrelatively narrow spectrum of unusually high pesticidal activity oninsects and acarids. Among the pests against which the compounds of thepresent invention are pesticidally effective are insects of the orderLepidoptera, Orthoptera, Heteroptera, Homoptera, Diptera, Coleoptera orHymenoptera, and acarids of the order Acarina including mites of thefamily Tetranychidae or Tarsonemidae and ticks such as Ornithodoros.

The compounds of the present invention can be used in combination withother pesticides such as the carbamates, phosphates and insect growthregulators, e.g. propoxur, carbaryl, naled, dichlorvos, methoprene,kinoprene, hydroprene, cyhexatin and resmethrin.

The compounds of the present invention of formula (IV) have plant growthregulating activity. They are useful also as intermediates in thesynthesis of the corresponding acids, which acids are utilized asstarting materials for synthetic pyrethroids. For example, an imidate offormula IV on treatment with an acid, e.g. sulfuric acid, generally atabove room temperature, affords the acid corresponding to the imidate(IV) which is then reacted with m-phenoxybenzyl alcohol or the like toform the desired synthetic pyrethroid such as permethrin, fenvalerate,fluvalinate and the like.

The following examples are provided to illustrate the practice of thepresent invention. Temperature is given in degrees Centigrade. RT meansroom temperature.

EXAMPLE 1

To a solution of 4.25 g (20 mmol) of 2-(4-chlorophenyl)-3-methylbutanoicacid in 30 ml of ether containing one drop of N,N-dimethylformamide isadded dropwise 3.81 g (30 mmol) of oxalyl chloride. The solution isstirred at RT until gas evolution ceases. The solvent and excess oxalylchloride are removed in vacuo and the residue is taken up in 30 ml ofether. This solution is then added dropwise at 0°-5° to 4.86 g (40 mmol)of a 14% w/w aqueous solution of ammonia. After stirring the mixture for30 minutes at 0°-5°, the aqueous layer is removed. The ethereal solutionis washed with water, dried over sodium sulfate, filtered andconcentrated in vacuo to obtain 2-(4-chlorophenyl)-3-methylbutyramide.

To a refluxing solution of 2.72 g (12.9 mmol) of2-(4-chlorophenyl)-3-methylbutyramide and 2.27 g (8.6 mmol) of3-phenoxybenzyl bromide in a solution of 15 ml dichloromethane and 3mlethyl ether is added a solution of 1.83 g (9.5 mmol) of silvertetrafluoroborate in ether. The mixture is refluxed for 2 hours and thenseparated by pouring into ice cold aqueous ethyl acetate/sodiumbicarbonate. The organic phase is washed with water, dried and strippedof solvent. The residue is triturated with ether and filtered. Thefiltrate is concentrated and chromatographed on silica gel, eluting with25% ethyl acetate/hexane, and then on plates using 35% ethylacetate/hexane, to yield 3-phenoxybenzyl2-(4-chlorophenyl)-3-methylbutanimidate, MS m/e 393 (M⁺).

EXAMPLE 2

Following the methods of Example 1, 2-(4-chlorophenyl)-3-methylbutanoicacid is reacted with oxalyl chloride and aqueous methylamine to giveN-methyl-2-(4-chlorophenyl)-3-methylbutyramide, which is then combinedwith 3-phenoxybenzyl bromide and AgBF₄, yielding 3-phenoxybenzylN-methyl-2-(4-chlorophenyl)-3-methylbutanimidate, MS m/e 407 (M⁺).

EXAMPLE 3

Using Example 1 procedures, each of the amides of column I, made byreaction of the corresponding carboxylic acid with ammonia and oxalylchloride, is reacted with 3-phenoxybenzyl bromide to yield the imidateof column II.

I

2-(4-trifluoromethylphenyl)-3-methylbutyramide

2-(4-fluorophenyl)-3-methylbutyramide

2-phenyl-3-methylbutyramide

2-[4-(difluoromethoxy)pheny]-3-methylbutyramide

II

3-phenoxybenzyl 2-(4-trifluoromethylphenyl)-3-methylbutanimidate

3-phenoxybenzyl 2-(4-fluorophenyl)-3-methylbutanimidate

3-phenoxybenzyl 2-phenyl-3-methylbutanimidate

3-phenoxybenzyl 2-[4-(difluoromethoxy)phenyl]-3-methylbutanimidate

EXAMPLE 4

The compound 2-(4-chlorophenyl)-3-methylbutanoic acid is reacted, as inExample 1, with oxalyl chloride and each of aqueous ethylamine, aqueousaniline and aqueous 4-chloroaniline to give, respectively,N-ethyl-2-(4-chlorophenyl)-3-methylbutyramide,N-phenyl-2-(4-chlorophenyl)-3-methylbutyramide, andN-(4-chlorophenyl)-2-(4-chlorophenyl)-3-methylbutyramide.

Each of the above amides is reacted with 3-phenoxybenzyl bromide andAgBF₄, yielding 3-phenoxybenzylN-ethyl-2-(4-chlorophenyl)-3-methylbutanimidate,N-phenyl-2-(4-chlorophenyl)-3-methylbutanimidate andN-(4-chlorophenyl)-2-(4-chlorophenyl)-3-methylbutanimidate, respectively

EXAMPLE 5

Following the method of Example 1,3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropaneamide, from3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid, oxalylchloride and ammonia, is reacted with 3-phenoxybenzyl bromide to give3-phenoxybenzyl 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanimidate.

EXAMPLE 6

A. A solution of 3.86 g (20 mmol) of2-(4-chlorophenylamino)-3-methylbutyronitrile in 10 ml of methanol issaturated at reflux with hydrogen chloride gas. When all of the startingnitrile has been consumed, most of the methanol and excess hydrogenchloride is removed in vacuo. Ether is added to precipitate thehydrochloride of methyl 2-(4-chlorophenyl)-3-methylbutanimidate, whichis isolated by filtration under nitrogen. The white solid is added withvigorous stirring to an ice-cold mixture of ether and aqueous sodiumbicarbonate. The aqueous layer is discarded, and the ethereal layer iswashed with cold water and dried over sodium sulfate. Filtration andconcentration in vacuo gives methyl2-(4-chlorophenylamino)-3-methylbutanimidate.

B. A solution of 2.25 g (10 mmol) of methyl 2-(4-chlorophenylamino)-3-methylbutanimidate and 4.00 g (20 mmol) of3-phenoxybenzyl alcohol is heated with continuous removal of methanol.Upon cessation of methanol evolution, there is obtained an oil,3-phenoxybenzyl 2-(4-chlorophenylamino)-3-methylbutanimidate.

EXAMPLE 7

Following the procedure described in Example 6, 2-(2-chloro-4-trifluoromethylphenylamino)-3-methylbutyronitrile isreacted with methanol and hydrogen chloride to give methyl2-(2-chloro-4-trifluoromethylphenylamino)-3-methylbutanimidate, which isthen reacted with 3-phenoxybenzyl alcohol, yielding the desired compound3-phenoxybenzyl2-(2-chloro-4-trifluoromethylphenylamino)-3-methylbutanimidate.

In like manner, each of the imidates of column III, made from thecorresponding nitrile, methanol and HCl, is reacted with 3-phenoxybenzylalcohol to give the esters of column IV.

III

methyl 2-phenylamino-3-methylbutanimidate

methyl 2-(2-fluoro-4-trifluoromethylphenylamino)-3-methylbutanimidate

methyl 2-(2,3,4,5-tetrafluorophenylamino)-3-methylbutanimidate

methyl 2-(4-chloro-2-fluorophenylamino)-3-methylbutanimidate

methyl2-(6-chloro-2-fluoro-4-trifluoromethylphenylamino)-3-methylbutanimidate

IV

3-phenoxybenzyl 2-phenylamino-3-methylbutanimidate

3-phenoxybenzyl2-(2-fluoro-4-trifluoromethylphenylamino)-3-methylbutanimidate

3-phenoxybenzyl 2-(2,3,4,5-tetrafluorophenylamino)-3-methylbutanimidate

3-phenoxybenzyl 2-(4-chloro-2-fluorophenylamino)-3-methylbutanimidate

3-phenoxybenzyl2-(6-chloro-2-fluoro-4-trifluoromethylphenylamino)-3-methylbutanimidate

EXAMPLE 8

A. To a mixture of 2.32 g (11 mmol) of2-(4-chlorophenyl)-3-methylbutyramide in methylene chloride is added, atroom temperature, 1.78 g (12 mmol) of trimethyloxoniumtetrafluoroborate. After stirring overnight under nitrogen, theresulting solution is poured onto an ice-cold mixture of ether andaqueous sodium bicarbonate. The aqueous layer is discarded, and theethereal layer is washed with cold water and dried over sodium sulfate.Filtration and concentration in vacuo affords methyl2-(4-chlorophenyl)-3-methylbutanimidate.

Following the procedure of Example 6B, 3-phenoxybenzyl alcohol andmethyl 2-(4-chlorophenyl)-3-methylbutanimidate are reacted to yield3-phenoxybenzyl 2-(4-chlorophenyl)-3-methylbutanimidate.

B. In like manner, each of2-(2-chloro-4-trifluoromethylphenyl)-3-methylbutyramide and3-(1,2-dibromo-2,2-dichloroethyl)-2,2-dimethylcyclopropaneamide isreacted with trimethyloxonium tetrafluoroborate, giving methyl2-(2-chloro-4-trifluoromethylphenyl)-3-methylbutanimidate and methyl2-(1,2-dibromo-2,2-dichloroethyl)-2,2-dimethylcyclopropanimidate,respectively. Each of these imidates is then reacted with3-phenoxybenzyl alcohol to yield, respectively, 3-phenoxybenzyl2-(2-chloro-4-trifluoromethylphenyl)-3-methylbutanimidate and3-phenoxybenzyl2-(1,2-dibromo-2,2-dichloroethyl)-2,2-dimethylcyclopropanimidate.

EXAMPLE 9

Each of the compounds under column V is reacted with(6-phenoxy-2-pyridyl)methyl alcohol, using the method described inExample 6B, to give the corresponding ester under column VI.

V

methyl 2-(4-chlorophenyl)-3-methylbutanimidate

methyl 2-(2-chloro-4-trifluoromethylphenylamino)-3-methylbutanimidate

methyl 2-(2,2-dichloroethenyl)-2,2-dicyclopropanimidate

methyl 2-(1,2-dibromo-2,2-dichloroethyl)-2,2-dicyclopropanimidate

VI

(6-phenoxy-2-pyridyl)methyl 2-(4-chlorophenyl)-3-methylbutanimidate

(6-phenoxy-2-pyridyl)methyl2-(2-chloro-4-trifluoromethylphenylamino)-3-methylbutanimidate

(6-phenoxy-2-pyridyl(methyl2-(2,2-dichloroethenyl)-2,2-dicyclopropanimidate

(6-phenoxy-2-pyridyl)methyl2-(1,2-dibromo-2,2-dichloroethyl)-2,2-dicyclopropanimidate

Two groups of 10 each 0-24 hour III instar Heliothis virescens larvaewere treated with 1 μl of the compound 3-phenoxybenzyl2-(4-chlorophenyl)-3-methylbutanimidate, in acetone at five differentconcentrations by application to the dorsum of the thorax. Two groups of10 each are treated identifically with 1 μl acetone only as controls.Larvae are held individually in 30 ml plastic cups provided withartificial medium for 72 hours at 25° and 16 hr photoperiod. After 72hours the number of dead is calculated as a percentage of the totalnumber originally treated and then corrected for any mortality in thecontrol groups using Abbott's formula. The LD₅₀ of the compound was lessthan 0.5%.

The nitrile (V) can be prepared as described in copending applicationSer. No. 089,003, filed Oct. 29, 1979, now U.S. Pat. No. 4,226,802 thedisclosure of which is incorporated by reference.

What is claimed is:
 1. A compound of the following formula: ##STR8##wherein, R is hydrogen, lower alkyl, phenyl, or substituted phenylwherein phenyl is substituted at one, two, or three of the ring carbonatoms with a group selected from lower alkoxy, lower alkyl, lowerfluoroalkyl, lower alkenyl, lower haloalkenyl, lower alkenyloxy,halogen, nitro, cyano, and lower alkylthio; and ##STR9## where R³ islower alkyl, lower haloalkyl, lower alkenyl or lower haloalkenyl; and R⁴is the group ##STR10## in which t is zero, one, two, three or four; Y isindependently selected from hydrogen, lower alkyl, lower fluoroalkyl,lower alkoxy, lower alkylthio, lower alkylcarbonyl, loweralkoxycarbonyl, halogen, and lower fluoroalkylthio; and Z isindependently selected from the values of Y, cycloalkyl, and lowerfluoroalkoxy.
 2. A compound of the following formula, according to claim1: ##STR11##
 3. A compound of the following formula, according to claim1: ##STR12##
 4. The compound according to claim 2 wherein R⁴ is##STR13##
 5. The compound according to claim 4 wherein Z is chloro,fluoro, trifluoromethyl or difluoromethoxy and Z is in the paraposition.
 6. The compound according to claim 5 wherein R is hydrogen ormethyl.
 7. The compound according to claim 5 wherein R is hydrogen. 8.The compound according to claim 2 wherein R⁴ is ##STR14##
 9. Thecompound according to claim 8 wherein t is zero or one; Y is chloro orfluoro, and is in the ortho position; and Z is chloro, fluoro ortrifluoromethyl and is in the para position.
 10. The compound accordingto claim 9 wherein R is hydrogen or methyl.
 11. The compound accordingto claim 9 wherein R is hydrogen.
 12. The compound according to claim 3wherein R³ is 2,2-dichloroethenyl.
 13. The compound according to claim12 wherein R is hydrogen.
 14. The compound according to claim 3 whereinR³ is 1,2-dibromo-2,2-dichloroethyl.
 15. The compound according to claim14 wherein R is hydrogen.